D型钠尿肽对豚鼠胃窦环形肌自发性收缩活动的影响及机制探讨

Effect of dendroaspis natriuretic peptide on spontaneous contraction of gastric circular smooth muscle in guinea-pig and its mechanism

目的观察豚鼠胃内是否存在钠尿肽受体(NPR)并观察D型钠尿肽(DNP)对豚鼠胃动力的影响及其机制的研究。方法 NPR在胃内的分布用放射自显影技术检测;胃平滑肌的自发性收缩活动用四道生理记录仪器记录;用膜片钳技术的全细胞技术记录钙敏感钾电流[IK(Ca)]。结果钠尿肽受体存在于豚鼠胃底、胃体和胃窦。并在胃窦部密度最大。DNP抑制胃窦环形肌自发性收缩活动并呈现剂量依赖关系。DNP的这种抑制效应被鸟苷酸环化酶抑制剂LY83583所减弱而被cGMP敏感的磷酸酯酶抑制剂所增强。非选择性钾通道抑制剂TEA明显抑制DNP对豚鼠胃窦环形肌自发性收缩活动的抑制作用。10nM的DNP增加豚鼠胃窦环形肌上钙敏感钾通道。结论钠尿肽受体存在于豚鼠胃内并在胃窦部位分布密度最大,DNP明显抑制豚鼠胃窦环形肌自发性收缩活动。这种抑制效应可能通过cGMP途径实现并且钙敏感钾通道可能也参与此过程。

[ Objective ] To determine whether the natriuretic peptide receptor （NPR） is present in the stomach of guinea pigs and to investigate the effect of dendroaspis natriuretic peptide （DNP） on the gastrie motility of guinea pigs and its mechanism. [Methods] The distribution of the NPR was analyzed by autoradioimmunography. The spontaneous contraction of gastric antral circular muscles of guinea pigs was reeorded by a 4-channel physiograph. The whole cell patch-clamp technique was introduced to record calcium-activated potassium currents in the gastric myocytes isolated by collagenase. [ Results ] The NPR existed in the gastric fundus, gastric body, and gastric antrum of guinea pigs, and its density was largest in the gastrieantrum. DNP inhibited spontaneous contraction and exhibited a dose-dependent manner. The DNP-induced inhibition was diminished by LY83583 （a guanylate cyclase inhibitor） and was potentiated by zaprinast （a cGMP-sensitive phosphoesterase inhibitor）. The inhibitory effect of DNP on spontaneous contraction was also inhibited by tetraethylammonium （a non-selective potassium ehannel blocker）; 10 nmol/L DNP increased the calcium-activated potassium currents in the gastric circular myocytes of guinea pigs. [Conclusions] The NPR is the most common in the gastric antrum of guinea pigs. DNP significantly inhibits sastrie motility in the gastric antrum of guinea pigs. The inhibitory effect occurs via a cGMP-dependent pathway, and a calcium-activated potassium channel may be also involved in the relaxation induced by DNP in gastric antral circular smooth muscles.